Of all the sensory modalities possessed by vertebrates, the ability to sense mechanical force remains the least well understood at the cellular and molecular level. In the glabrous skin, touch is sensed by Meissner and Pacinian corpuscles ? the detectors of fine objects and minute skin deformations. The corpuscles are innervated by rapidly-adapting neuronal mechanoreceptors, which can directly convert touch into excitation, by an unknown mechanism. Here, we aim to elucidate this mechanism by studying the mechanosensitivity in rapidly-adapting mechanoreceptors, using the trigeminal system of the duck embryo as a model. Duck trigeminal ganglia contain a large proportion of rapidly-adapting mechanoreceptors, which innervate the numerous Meissner- and Pacinian-like corpuscles in the glabrous skin of the bill. Using this model, we aim to determine the role of stretch-sensitive cationic and voltage-sensitive sodium channels in the three principal processes of touch sensitivity: (1) the conversion of touch into excitatory current; (2) the generation of action potential, and (3) propagation of the rapidly-adapting afferent message along the axon. Our studies will reveal cellular and molecular principles underlying the sense of touch in rapidly-adapting neuronal mechanoreceptors.

Public Health Relevance

The sense of touch is a fundamental physiological capacity which allows us to interact with the environment through the perception of mechanical force. Our work will elucidate how mechanical force is perceived at the molecular level by neuronal mechanoreceptors. The proposed studies will obtain fundamental knowledge that will facilitate the development of novel pharmacological strategies to treat a range of neurological disorders associated with painful sensitivity in the skin.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS097547-01A1
Application #
9259461
Study Section
Neurotransporters, Receptors, and Calcium Signaling Study Section (NTRC)
Program Officer
Gnadt, James W
Project Start
2016-12-01
Project End
2021-11-30
Budget Start
2016-12-01
Budget End
2017-11-30
Support Year
1
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Yale University
Department
Physiology
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
Hoffstaetter, Lydia J; Mastrotto, Marco; Merriman, Dana K et al. (2018) Somatosensory Neurons Enter a State of Altered Excitability during Hibernation. Curr Biol 28:2998-3004.e3
Anderson, Evan O; Schneider, Eve R; Matson, Jon D et al. (2018) TMEM150C/Tentonin3 Is a Regulator of Mechano-gated Ion Channels. Cell Rep 23:701-708
Anderson, E O; Schneider, E R; Bagriantsev, S N (2017) Piezo2 in Cutaneous and Proprioceptive Mechanotransduction in Vertebrates. Curr Top Membr 79:197-217
Schneider, Eve R; Anderson, Evan O; Mastrotto, Marco et al. (2017) Molecular basis of tactile specialization in the duck bill. Proc Natl Acad Sci U S A 114:13036-13041